Is GDF1 p.Leu165= (c.493C>T) pathogenic?

GDF1 p.Leu165= (c.493C>T) is classified Likely benign in GDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). Very rare (popmax 0.00577%, nfe).

How common is GDF1 p.Leu165= (c.493C>T) in the general population?

GDF1 p.Leu165= (c.493C>T) is very rare (popmax 0.00577%, nfe) (gnomAD).

GDF1 p.Leu165=

c.493C>T · VCV3661284

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00577%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.9	GERP -1.1, phastCons 1
Overall
CADD	10.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00577% European (non-Finnish) · 62/1,073,752 alleles

Filtering AF 0.0046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00481% 66/1,373,062 alleles · very rare exomes 60/1,222,924 · genomes 6/150,138 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00577%	17,319
African / African-American	0.00465%	21,513
Remaining individualsnot grpmax-eligible	0.00193%	51,738

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GDF1
Protein: p.Leu165=
Coding: c.493C>T
MANE Select: NM_001492
Type: single nucleotide variant
Location: chr19:18869223 (GRCh38)

Full GDF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gdf1-p-leu165 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown